Against blood clots and cancer
A new reversible nonpharmacological method of antiplatelet therapy, developed by researchers from George Washington University under the guidance of Associate Professor Anne-Laure Papa, will reduce the risk of thrombosis during surgical interventions and prevent the metastasis of malignant tumors in patients undergoing chemotherapy.
Platelets play a major role in the process of forming blood clots and protecting the body from both small and life-threatening bleeding. However, platelet hyperactivity can contribute to the development of a number of pathologies, including severe thrombosis and cardiovascular diseases. Existing antiplatelet drugs contribute to the dissolution of blood clots, but their effect is very difficult to neutralize, which puts patients' lives in danger in cases of unexpected severe bleeding or if emergency surgery is necessary.
In addition to their main function, platelets are an important component of the metastasis process. They bind to malignant cells and protect them both from the immune system and from the physical stress accompanying circulation in the bloodstream. Platelets also contribute to the release of cancer cells from blood vessels into tissues and the formation of secondary tumors.
The approach proposed by the authors is to modify platelets to produce "deceptions" – empty platelets that can bind to certain cells, but do not trigger the aggregation process and do not perform other normal functions of platelets, including the release of chemical signals associated with the process of thrombosis.
To obtain deceptions, human platelets are treated with detergent and centrifuged, as a result of which they lose their internal structures and the ability to activate and aggregate. This process leads to a decrease in the size of platelets to about a third of their original size, but ensures the preservation of most of the adhesion receptors on their surface. This ensures their ability to bind to other cells without triggering the thrombosis process.
To study the effect of empty platelets on the formation of blood clots, the authors introduced them into a microfluidic chip simulating a blood vessel and observed reactions developing in response to various platelet-stimulating chemical compounds. By themselves, the modified platelets did not exhibit typical platelet behavior. At the same time, when mixed inside a microfluidic chip with human blood, they reduced the ability of platelets contained in it to aggregate and thrombosis. It is important to note the fact that the described effects, inhibiting the mechanisms of blood clotting, were quickly eliminated by the introduction of fresh platelets into the system.
The important role of platelets in metastasis prompted the authors to search for methods of using the approach they developed to influence circulating malignant cells. Empty platelets successfully competed with normal ones when binding to cancer cells and effectively prevented the latter from leaving the microfluidic simulator of the blood vessel. Moreover, in the metastasis model, the introduction of empty platelets simultaneously with cancer cells ensured a decrease in the number of secondary tumors forming.
The authors plan to improve the developed technology by increasing the circulation time of empty platelets compared to normal ones. In addition, their plans include studying the possibility of using empty platelets as carriers of drugs to affect diseases associated with these cells.
Article by Anne-Laure Papa et al. Platelet decoys inhibit thrombosis and prevent metastatic tumor formation in preclinical models published in the journal Science Translational Medicine.
Evgenia Ryabtseva, portal "Eternal Youth" http://vechnayamolodost.ru Based on materials from George Washington University: Researchers Develop Reversible, Drug-Free Antiplatelet Therapy to Fight Dangerous Blood Clots and Cancer Metastasis.